Effects of Purines, Pyrimidines, Nucleosides, and Chemically Related Compounds on the Cell Cycle

Wheeler, Glynn P.; Simpson-Herren, Linda

doi:10.1016/b978-0-12-781260-1.50015-x

Cited by 8 publications

(6 citation statements)

References 128 publications

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“…B huyan et al [3] have reported that when the survival fraction of asynchronously proliferating DON cells was plot ted against increasing concentrations of 7-deazaadenosine, the viable fraction exponentially decreased, a characteristic of agents not cell-cy cle-stage-specific. These results (table III, IV) [3] suggest that 7-deazaadenosine and 2-fluoroadenosine have additional loci for the production of a lethal lesion in addition to the inhibition of de novo purine synthesis [1,16,17,23,33], Perhaps this involves incorporation into RNA [23,33].…”

Section: Discussionmentioning

confidence: 99%

“…Although TG, MMPR, Ara-MP, and 9-ethyl-MP may inhibit the synthesis and function of both DNA and RNA, the effects may be greater with respect to DNA. However, since TG and MMPR inhibit the de novo synthesis of purine nucleotides, these agents would not necessarily cause unbalanced growth [33], In fact, it has been reported that TG prevents thymineless death in bacteria [18].…”

Section: Discussionmentioning

confidence: 99%

“…6-Thiopurine, as well as TG and MMPR, blocks or delays cells in Gt and S phases from proceeding to mitosis [32], Furthermore, TG is incorporated into DNA and RNA, and, to a limited extent, MP is converted into 6-thioguanylic acid, which is then incorporated into DNA [17,33]. Since 6-thioguanylic acid is a considerably weaker pseudofeedback inhibitor than the ribonu cleotides of MP and MMPR, the greater toxicity of TG must be due to other mechanisms [33]. The cytotoxicity of MP and TG for lymphoma L5178Y cells in culture may be due to incorporation of MP (as TG deriv atives) and TG into DNA [28,29].…”

Section: Discussionmentioning

confidence: 99%

“…Since the purine analogs can act at multiple sites in the cell, their action may not be limited to cells in the process of synthesizing DNA [33], and they would be expected to have optimal in vivo dose schedules different from those of S-phase specific agents, e.g., Ara-C or hydroxyu rea [24], Schedule dependency studies using BDF1 mice implanted with leukemia L1210 (105 cells implanted i.p. ; treatment beginning on day 2 after implant) have shown that purine analogs require no particular schedule.…”

Section: Discussionmentioning

confidence: 99%

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Kinetics of Reduction in Viability of Cultured Leukemia L1210 Cells Exposed to Purine Analogs

Wilkoff¹,

Dulmadge²,

Lloyd³

1977

Chemotherapy

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Rates of reduction in viability and degree of cell killing were relatively independent of concentrations when replicating cultured L1210 cells were exposed to increasing concentrations of 6-thioguanine, 6-methylthiopurine ribonucleoside, 9-β-D-arabinofuranosyl-9H-purine-6-thiol, or 9-ethyl-6-thiopurine. The relative lack of dependence of cell killing rate on cytotoxic concentrations suggest (a) that these agents may be only effective against proliferating cells, and (b) that only limited therapeutic advantage can be gainged by increasing their concentration beyond a minimum effective level. In contrast, the rate and degree of cell killing were dependent upon concentrations when cells were exposed to increasing amounts of 4-aminopyrrolo(2,3-d)pyrimidine-β-D-ribofuranoside or to 2-fluoroadenosine, indicating that these analogs are not cell-cycle-stage-specific and that nonreplicating cell populations may be sensitive to them.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Kinetics of Reduction in Viability of Cultured Leukemia L1210 Cells Exposed to Purine Analogs

Wilkoff¹,

Dulmadge²,

Lloyd³

1977

Chemotherapy

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“…There is a general agreement (Wheeler and Simpson-Herren, 1973;Clarkson, 1974;Valeriote and van Putten, 1975) that the faster the growth of a cell population, the greater is the susceptibility of that population to the cytocidal effects of antimetabolites. Indeed, numerous experimental data obtained on various cell systems definitely show that proliferating cells are altogether more sensitive to cytotoxic agents than resting cells (Bruce, Meeker and Valeriote, 1966;van Putten, Lelieveld and Kram-Jdsenga, 1972;Rajewsky, 1975).…”

mentioning

confidence: 99%

Responses of proliferating and non-proliferating Chinese hamster cells to cytotoxic agents

Epifanova¹,

Smolenskaya²,

Polunovsky³

1978

Br J Cancer

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Summary.-The effects of various cytotoxic chemicals, as measured by viable cell counts, colony-forming ability and proliferative capacity, have been studied using Chinese hamster cells in exponential and plateau (stationary) phases of growth. The proliferating cells were altogether more sensitive to the action of the drugs than nonproliferating cells. However, imuran (azathioprine) a purine antimetabolite, was more effective against the plateau-phase cells. The observed response of cells to imuran could be detected at a wide range of concentrations (1-100 ,ug/ml). These findings are discussed in view of the possible ability of imuran to interfere with active metabolic processes in non-proliferating cells.

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Parameters for growth of the imaginal wing disk in last instar larvae of Galleria mellonella L

1980

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In last instar larvae of Galleria mellonella, the observed increase in the number of cells of growing intact imaginal wing disks was completely blocked by ligation of the mesothorax and stimulated again by external applications of low and high doses (2.6 to 130 Kglg) of ecdysterone. However, at no hormonal dose applied has the full extent of normal wing growth been attained. The ecdysteroid dependent cuticle synthesis could be induced in disks of various sizes. The cell number of imaginal disks of young last or supernumerary instar larvae is exponentially correlated with the body weight. The rates of cell division during prepupal development of the wing disk appeared to be about the same in last and supernumerary instar larvae.In normal pupae the borders of the everted wings are fitted precisely to a cuticular demarcation line on the underlying abdomen. X-ray irradiations of last instar larvae led to a reduction of the pupal wing surface and cell number, but did not affect the position of the demarcation line. The X-ray experiments confirm the finding that reduced wings are capable of normal pupal cuticle synthesis.

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Effects of Purines, Pyrimidines, Nucleosides, and Chemically Related Compounds on the Cell Cycle

Cited by 8 publications

References 128 publications

Kinetics of Reduction in Viability of Cultured Leukemia L1210 Cells Exposed to Purine Analogs

Kinetics of Reduction in Viability of Cultured Leukemia L1210 Cells Exposed to Purine Analogs

Responses of proliferating and non-proliferating Chinese hamster cells to cytotoxic agents

Parameters for growth of the imaginal wing disk in last instar larvae of Galleria mellonella L

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